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High prevalence of subclass-specific binding and neutralizing antibodies against Clostridium difficile toxins in adult cystic fibrosis sera: possible mode of immunoprotection against symptomatic C. difficile infection

Monaghan, Tanya M.; Negm, Ola H.; MacKenzie, B.; Hamed, Mohamed R.; Shone, Clifford C.; Humphreys, D.P.; Acharya, K. Ravi; Wilcox, Mark H.

Authors

Tanya M. Monaghan tanya.monaghan@nottingham.ac.uk

Ola H. Negm ola.negm@nottingham.ac.uk

B. MacKenzie

Mohamed R. Hamed

Clifford C. Shone

D.P. Humphreys

K. Ravi Acharya

Mark H. Wilcox



Abstract

Objectives: Despite multiple risk factors and a high rate of colonization for Clostridium difficile, the occurrence of C. difficile infection in patients with cystic fibrosis is rare. The aim of this study was to compare the prevalence of binding C. difficile toxin-specific immunoglobulin (Ig)A, IgG and anti-toxin neutralizing antibodies in the sera of adults with cystic fibrosis, symptomatic C. difficile infection (without cystic fibrosis) and healthy controls.

Methods: Subclass-specific IgA and IgG responses to highly purified whole C. difficile toxins A and B (toxinotype 0, strain VPI 10463, ribotype 087), toxin B from a C. difficile toxin-B only expressing strain (CCUG 20309) and precursor form of B fragment of binary toxin, pCDTb, were determined by protein microarray. Neutralizing antibodies to C. difficile toxins A and B were evaluated using a Caco-2 cell-based neutralization assay.

Results: Serum IgA anti-toxin A and B levels and neutralizing antibodies against toxin A were significantly higher in adult cystic fibrosis patients (n=16) compared with healthy controls (n=17) and patients with symptomatic C. difficile infection (n=16); p≤0.05. The same pattern of response prevailed for IgG, except that there was no difference in anti-toxin A IgG levels between the groups. Compared with healthy controls (toxins A and B) and patients with C. difficile infection (toxin A), sera from cystic fibrosis patients exhibited significantly stronger protective anti-toxin neutralizing antibody responses.

Conclusion: A superior ability to generate robust humoral immunity to C. difficile toxins in the cystic fibrosis population is likely to confer protection against symptomatic C. difficile infection. This protection may be lost in the post-transplantation setting, where sera-monitoring of anti-C. difficile toxin antibody titers may be of clinical value.

Journal Article Type Article
Publication Date Jul 19, 2017
Journal Clinical and Experimental Gastroenterology
Print ISSN 1178-7023
Electronic ISSN 1178-7023
Publisher Dove Medical Press
Peer Reviewed Peer Reviewed
Volume 10
APA6 Citation Monaghan, T. M., Negm, O. H., MacKenzie, B., Hamed, M. R., Shone, C. C., Humphreys, D., …Wilcox, M. H. (2017). High prevalence of subclass-specific binding and neutralizing antibodies against Clostridium difficile toxins in adult cystic fibrosis sera: possible mode of immunoprotection against symptomatic C. difficile infection. Clinical and Experimental Gastroenterology, 10, https://doi.org/10.2147/CEG.S133939
DOI https://doi.org/10.2147/CEG.S133939
Keywords Clostridium difficile, Cystic fibrosis, Antibodies
Publisher URL https://www.dovepress.com/high-prevalence-of-subclass-specific-binding-and-neutralizing-antibodi-peer-reviewed-article-CEG
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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